Li R, Huang L, Guo H, Toole B P
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
J Cell Physiol. 2001 Mar;186(3):371-9. doi: 10.1002/1097-4652(2000)9999:999<000::AID-JCP1042>3.0.CO;2-8.
Analysis of basigin-null mice has shown that basigin is involved in several important physiological processes including reproductive, immune, and neural activities (Igakura et al., 1998, Dev Biol 194:152-165). However, its molecular mechanism of action in these processes has not yet been established. Our objective here is to determine whether basigin has functional properties similar to its apparent human tumor cell homolog, EMMPRIN, i.e., the ability to stimulate matrix metalloproteinase (MMP) production in fibroblasts (Guo et al. 1997, J Biol Chem 272:24-27). Mouse cells express two major forms of basigin that differ in their degree of glycosylation (molecular weights: 45 and 58 kDa) but, in similar fashion to human EMMPRIN, mouse tumor cells express higher levels of basigin than normal cells. We have used three different methods to show that basigin stimulates MMP expression in fibroblasts. First, recombinant basigin was partially purified from transfected CHO cells by affinity chromatography. This basigin preparation stimulates production of MMPs on addition to fibroblasts in culture. Second, co-culture of basigin-transfected CHO cells with fibroblasts gives rise to increased expression of MMPs as compared to control co-cultures. Third, we employed a novel approach in which a recombinant basigin adenovirus was constructed and used to infect the target fibroblasts, so that mutual stimulation between neighboring fibroblasts would be expected to result. In this method also, basigin stimulates production of MMPs. Finally, we showed that addition of basigin or EMMPRIN antibody, respectively, to recombinant basigin or EMMPRIN adenovirus-infected cells augments stimulation of MMP synthesis, implying that cross-linking of basigin/EMMPRIN in the membrane enhances activity. We conclude that murine basigin and human EMMPRIN have similar MMP-inducing activities and are functional homologs.
对缺乏基底细胞黏附分子（basigin）的小鼠的分析表明，基底细胞黏附分子参与了包括生殖、免疫和神经活动在内的多个重要生理过程（Igakura等人，1998年，《发育生物学》194:152 - 165）。然而，其在这些过程中的分子作用机制尚未明确。我们在此的目标是确定基底细胞黏附分子是否具有与其明显的人类肿瘤细胞同源物——细胞外基质金属蛋白酶诱导因子（EMMPRIN）相似的功能特性，即刺激成纤维细胞中基质金属蛋白酶（MMP）产生的能力（Guo等人，1997年，《生物化学杂志》272:24 - 27）。小鼠细胞表达两种主要形式的基底细胞黏附分子，它们的糖基化程度不同（分子量分别为45和58 kDa），但与人类EMMPRIN类似，小鼠肿瘤细胞中基底细胞黏附分子的表达水平高于正常细胞。我们使用了三种不同的方法来证明基底细胞黏附分子能刺激成纤维细胞中MMP的表达。第一，通过亲和层析从转染的中国仓鼠卵巢（CHO）细胞中部分纯化重组基底细胞黏附分子。将这种基底细胞黏附分子制剂添加到培养的成纤维细胞中能刺激MMP的产生。第二，将转染了基底细胞黏附分子的CHO细胞与成纤维细胞共培养，与对照共培养相比，MMP的表达增加。第三，我们采用了一种新方法，构建重组基底细胞黏附分子腺病毒并用于感染目标成纤维细胞，预期相邻成纤维细胞之间会产生相互刺激。在这种方法中，基底细胞黏附分子也能刺激MMP的产生。最后，我们表明分别向重组基底细胞黏附分子或EMMPRIN腺病毒感染的细胞中添加基底细胞黏附分子或EMMPRIN抗体，会增强对MMP合成的刺激，这意味着膜上基底细胞黏附分子/EMMPRIN的交联增强了活性。我们得出结论，小鼠基底细胞黏附分子和人类EMMPRIN具有相似的诱导MMP的活性，并且是功能同源物。
